1. Field of the Invention
The present invention provides an improved method and apparatus having improved sensitivity and detection of multiple ions produced from an evaporated sample in an RF-only quadrupole ion source in a carrier gas. The ions are optionally focused and are then conveyed to a RF/DC quadrupole mass spectrometer and are analyzed and detected to produce a mass spectrum. The present invention also concerns the improved sensitivity and improved detection of ions using gas chromatography coupled with mass spectrometry (GC-MS). In particular, the improved method relates to the injection of a sample of a neutral gas, preferably from a gas chromatograph, into a first radio-frequency (RF)-only controlled quadrupole which contains a carrier gas, such as helium, followed by ionization of the gas sample. The produced ions are then conveyed to an RF and direct current (DC) quadrupole mass spectrometer, and the ions passing through this quadrupole are detected in order to produce a mass spectrum.
2. Description of Related Art
It is well known that ion transmission and mass resolution in a quadrupole mass filter analyzer are related to the phase space distribution of ions entering the quadrupole mass filter. If the phase space distribution is larger than the phase space acceptance ellipse of the quadrupole mass filter, only a portion of the ions can pass through the mass analyzer. In an x,y,z coordinate system for a quadrupole, the z axis is essentially the central axis within the space created by the quadrupole electrodes. In the traditional GC-MS ion source, most ions are formed off the z axis. Though sophisticated static lenses help to focus the ions to near the z axis, only a small portion of the ions fall inside of the phase space acceptance ellipse; thus, only a small portion of the ions pass through the mass filter analyzer for detection. Space charges, especially the higher ion concentration of carrier gas in a GC-MS mass spectrometer system, further prevent ions from being focused to near the z axis.
Methods which improve resolution in quadrupole mass filters have been used in the collision induced dissociation of mass spectrometry/spectrometry (MS/MS). The focus effect of collision damping in a quadrupole field is well known. See G. C. Stafford et al., U.S. Pat. No. 4,540,884 and D. J. Douglas et al., Journal American Society for Mass Spectrometry, Vol. 3, p. 398, (1992). Douglas et al., in U.S. Pat. No. 5,248,875, titled "The Method for Increased Resolution in Tandem Mass Spectrometry", propose to focus fragment ions of collision induced dissociation (CID) with a high pressure collision cell, composed of an RF quadrupole field. As a result, transmission rates and mass resolution of fragment ions in the third quadrupole mass analyzer are increased.
A more detailed discussion of this prior art is helpful to show the advance of the improved method of the present invention.
U.S. Pat. No. 5,248,875--FIG. 1 herein is FIG. 1 from U.S. Pat. No. 5,248,875 which issued on Sep. 28, 1993 and shows in schematic representation the prior art triple quadrupole mass spectrometer 10. It is commercially available from SCIEX DIVISION of MDS Health Group Limited of Thornhill, Ontario, Canada, under the trademark API IV and the Perkin Elmer Corp. of Norwalk, Conn. The mass spectrometer 10 has a conventional ion source 12 which produces ions and directs the ions to an inlet chamber 14. These ions in chamber 14 are directed through orifice 16, a gas curtain chamber 18 (see, e.g., U.S. Pat. No. 4,137,750), a set of RF only rods 20 as a transportation component and then through first, second and third quadrupoles Q1, Q2, and Q3 respectively. As is conventional, quadrupole Q1 and Q3 each have both RF and DC applied between their respective opposing pairs of rods and act as mass filters. Quadrupole Q2 is of an open structure (formed from wires) and has RF only applied to its rods.
The primary advance of U.S. Pat. No. 5,248,875 is the enclosing of quadrupole Q2 in a container as is shown as its FIG. 8 and is shown herein as FIG. 6. In FIG. 6 the quadrupole Q2 is enclosed in a container (shell) 50 so that the pressure or gas from source 22 can be controlled independently from the pressure or gas of the remainder of the system. The quadrupole rods 24 (or 24A) of Q2 may be solid rods. Container 50 has entrance aperature 52 and exit port cylindrical body 55. Aperature 52 and 54 are electrically isolated from each other and from the body 55. The pressure in shell 50 is controlled by changing the size of the aperture 52 and 54.
In the first quadrupole Q1, the desired parent ions are selected, by setting an appropriate magnitude and a ratio of RF to DC on its rods. In a second quadrupole Q2, collision gas from source 22 is sprayed across the rods 24 of quadrupole Q2 to create a collision cell in which the parent ions entering Q2 are fragmented by collision with the added gas. Q3 serves as a mass analyzing device and is scanned to produce the desired mass spectrum. Ions which pass through Q3 are detected at detector 26. The ions impinging upon detector 26 are used to create the well known mass spectrum.
The quadrupoles Q1, Q2, and Q3 and RF only rods 20 are optionally housed in a chamber 27 which is evacuated by a cryopump 28 having a cryosurface 29 encircling rods 20 and another cryosurface 30 encircling Q2. It is noted that while FIG. 1 illustrates a typical presently available commercial MS instrument which is competitive with other available triple quadrupole mass spectrometers, the details of construction can of course vary somewhat. For instance, conventional vacuum pumps can be used instead of cryopumps. This patent does not teach or suggest the introduction of a charge-neutral sample into a quadrupole for ionization and focusing.
Douglas et al.,--In FIG. 2 herein (taken from FIG. 1 of J. Amer. Soc. Mass. Spec., Vol. 3, p. 399 (1992)), the analyzing system is shown as 100. Ions are sampled from an atmospheric ion (API) source 112 (either a corona discharge or an ion spray), through opening 116 through nitrogen curtain gas in area 118 through sampling opening 19 into a region 19A containing an RF quadrupole Q0. Daughter ions are produced within region 19A in quadrupole Q0 which pass through the interquad aperture IQ into the RF and DC analyzing quadrupole mass spectrometer Q1. The ions are detected at Y0. Ion counting is used and the mass spectra are collected and created in a commercial multichannel scaler. Diffusion pumps DP1 and DP2 are used to obtain the vacuum of 5.times.10.sup.-6 to 3.times.10.sup.-5 torr. A backup pump BP is used to maintain a useful vacuum at all times. This reference does not teach or suggest the introduction of a charge-neutral sample into a quadrupole for ionization and focusing.
In a conventional quadrupole mass filter, as a consequence of the oscillating field, a positive ion injected into the quadrupole region will oscillate between the adjacent electrodes of opposite polarity. At a specified radio frequency (RF) and specified magnitudes of RF and DC, ions of a given mass undergo stable oscillation between the electrodes. Ions of higher or lower mass undergo oscillation of increasing amplitude until they collide on the quadrupole electrodes and are not detected further. The ion with a stable oscillation continues at its original velocity down the flight path of the quadrupole to the collector/multiplier for detection and analysis.
In theory, the resolution of a quadrupole mass filter can be increased to a high value by selecting the ratio of the constant DC component to a radio frequency (U/V.sub.0) where U is defined as the DC amplitude in volts applied between opposite pairs of electrodes, and V.sub.0 is defined as the radio frequency amplitude in volts, close to the apex of the stability region. In practice, however, a significant percentage of the selected ions oscillate with a significant amplitude to strike a quadrupole electrode and thus reduce the efficiency of the transmission. The errant motion depends on a number of factors, such as the velocity component in the x and y direction and upon the position at which the ion enters the quadrupole electrode cavity. Also, the alignment of the electrodes must be very precise and the electrodes must be free from any non-conducting film (such as pump oil, excess condensation and the like) that would distort the symmetric field.
For a review of this field, see R. E. March and R. J. Hughes, Quadrupole Storage Mass Spectrometry, published by John Wiley & Sons, New York, N.Y. in 1989.
Additional related art of interest includes, for example:
S. C. Davis et al., in 1990 in Rapid Communications in Mass Spectrometry, Vol. 4, pp. 186 to 197 disclose computer modelling of fragmentation processes in radio-frequency multiple collision cells. Ions are injected into and through the cell into an MS/MS instrument.
M. Morris et al., in 1993 in Rapid Communications in Mass Spectrometry, Vol. 7, pp. 1136 to 1140 disclose triple quadrupole mass spectrometry of low-energy ion/molecule products from collision with ammonia.
M. Morris et al., in 1994 in the Journal of the American Society of Mass Spectrometry, Vol. 5, pp. 1042 to 1063 disclose an RF-only quadrupole collision cell for use in tandem mass spectrometry as a component of a triple quadrupole mass spectrometer.
B. A. Thomson et al., in 1995 in Analytical Chemistry, Vol. 67, No. 10, pp. 1696 to 1704 disclose improved collisionally activated dissolution efficiency and mass resolution using a triple quadrupole mass spectrometer.
K. Whelan et al., in 1995 in Rapid Communications in Mass Spectrometry, Vol. 9, pp. 1366 to 1375 disclose ion dissociation reactions included in a high pressure quadrupole collision cell for a triple quadrupole mass spectrometer system.
None of these patents or articles individually or collectively teach or suggest the present invention.
All articles, references, patents, patent applications, provisional patent applications, standards, and the like cited herein are incorporated by reference in their entirety.
As can be seen from the discussion herein, a need exists for a simple method and apparatus to ionize a neutral gas sample in a carrier gas within an RF-only quadrupole followed by collection and detection using a RF/DC quadrupole mass spectrometer. The present invention provides a solution for this need.